Endoscopic Disease Research Articles

Baseline Patient-reported Symptoms Less Predictive Than MM-SES-CD for Endoscopic Remission in Crohn's Disease.

This analysis evaluates the association between baseline patient-reported symptom (PRS) severity in Crohn's disease (CD), including abdominal pain, stool frequency, general well-being, and achievement of clinical and endoscopic outcomes. We compared baseline PRS to baseline endoscopic scores for the prediction of endoscopic remission (ER). This post hoc analysis of 2 clinical trials of infliximab in CD included 601 patients and evaluated baseline PRS variables (abdominal pain, stool frequency, and general well-being) as measured by the Crohn's disease activity index and their association with 6-month clinical remission (CR) (Crohn's Disease Activity Index<150), corticosteroid-free CR, and week 26/54 ER (absence of mucosal ulceration). Logistic regression models assessed the relationships between PRS and outcomes of interest. Receiver operating characteristic curve analyses compared the sensitivity and specificity of the different baseline PRS compared with baseline endoscopic scores for achievement of ER at weeks 26 and 54. No difference was found comparing patients with higher baseline PRS to those with lower PRS in achieving 6-month CR, 6-month corticosteroid-free CR, or week 26/54 ER. Modified multiplier of the SES-CD (MM-SES-CD) at baseline demonstrated a significant ability to predict week 54 ER (area under the curve, 0.71; 95% CI 0.65-0.78; P =0.017). Baseline PRS in CD is not prognostic of clinical or endoscopic response. In contrast, active endoscopic disease as measured by the MM-SES-CD, more accurately predicts endoscopic outcomes. Endoscopic scores such as the MM-SES-CD may be considered for selection criteria and as a primary outcome of interest in CD trials, with PRS as a co-primary or secondary endpoint.

Can balloon-assisted enteroscopy predict disease outcomes in patients with small-bowel Crohn’s disease?

There are limited studies on the endoscopic assessment of disease activity using balloon-assisted enteroscopy (BAE) and its predictive role for long-term outcomes of patients with small bowel Crohn’s disease (CD). We sought to investigate the value of BAE as a predictor of long-term outcomes in patients with small-bowel CD. A total of 111 patients with small-bowel CD whose endoscopic disease activity was assessed using BAE based on the small-bowel simple endoscopic score for Crohn’s disease (small-bowel SES-CD) at Samsung Medical Center were retrospectively selected from January 2014 to August 2020. The outcome was an evaluation of the risk of surgery according to a small-bowel SES-CD of 0–6 vs. ≥ 7 and endoscopic findings (presence of any ulcer and degree of stricture) using the Cox proportional hazards model. The risk of surgery was significantly increased in patients with a small-bowel SES-CD of ≥ 7 compared to a small-bowel SES-CD of 0–6 [hazard ratio (HR) 6.31; 95% confidence interval (CI) 1.48–26.91; p = 0.013]. In addition, the risk of surgery was significantly increased in patients with stenosis with “cannot be passed” compared to the cases without stenosis (HR 12.34; 95% CI 1.66–91.92; p = 0.014), whereas there was no significance in any ulcer. The present study demonstrated the role of BAE in the endoscopic assessment of disease activity and its predictive value for the risk of surgery in small-bowel CD patients. Further optimization of BAE utilization for the assessment of disease activity is warranted in clinical practice.

Body composition parameters correlate with the endoscopic severity in Crohn's disease patients treated with infliximab.

The disease activity status and behavior of Crohn's disease (CD) can reflect the severity of the disease, and changes in body composition are common in CD patients. The aim of this study was to investigate the relationship between body composition parameters and disease severity in CD patients treated with infliximab (IFX). Patients with CD assessed with the simple endoscopic score (SES-CD) and were treated with IFX were retrospectively collected, and body composition parameters at the level of the 3rd lumbar vertebrae were calculated from computed tomography (CT) scans of the patients. The correlation of patients' body composition parameters with disease activity status and disease behavior was analyzed, and the diagnostic value of the relevant parameters was assessed using receiver operating characteristic (ROC) curves. A total of 106 patients were included in this study. There were significant differences in the subcutaneous adiposity index (SAI) (p = 0.010), the visceral adiposity index (VAI) (p < 0.001), the skeletal muscle mass index (SMI) (p < 0.001), and decreased skeletal muscle mass (p < 0.001) among patients with different activity status. After Spearman and multivariate regression analysis, SAI (p = 0.006 and p = 0.001), VAI (p < 0.001 and p < 0.001), and SMI (p < 0.001and p = 0.007) were identified as independent correlates of disease activity status (both disease activity and moderate-to-severe activity), with disease activity status independently positively correlated with SAI and SMI and independently negatively correlated with VAI. In determining the disease activity and moderate-to-severe activity status, SMI performed best relative to SAI and VAI, with areas under the ROC curve of 0.865 and 0.801, respectively. SAI (p = 0.015), SMI (p = 0.011) and decreased skeletal muscle mass (p = 0.027) were significantly different between different disease behavior groups (inflammatory disease behavior group, complex disease behavior group) but were not independent correlates (p > 0.05). Body composition parameters of CD patients treated with IFX correlate with the endoscopic disease severity, and SMI can be used as a reliable indicator of disease activity status.

Adalimumab Clearance, Rather Than Trough Level, May Have Greatest Relevance to Crohn's Disease Therapeutic Outcomes Assessed Clinically and Endoscopically.

We postulated that adalimumab [ADA] drug clearance [CL] may be a more critical determinant of therapeutic outcome than ADA concentration. This was tested in Crohn's disease [CD] patients undergoing ADA maintenance treatment. CD patients from four cohorts received ADA induction and started maintenance therapy. Therapeutic outcomes consisted of endoscopic remission [ER], sustained C-reactive protein [CRP] based clinical remission [defined as CRP levels below 3 mg/L in the absence of symptoms], and faecal calprotectin [FC] level below 100 µg/g. Serum albumin, ADA concentration, and anti-drug antibody status were determined using immunochemistry and homogeneous mobility shift assay, respectively. CL was determined using a nonlinear mixed effect model with Bayesian priors. Statistical analysis consisted of Mann-Whitney test and logistic regression with calculation of odds ratio. Repeated event analysis was conducted using a nonlinear mixed effect model. In 237 enrolled patients [median age 40 years, 45% females], median CL was lower in patients achieving ER as compared with those with persistent active endoscopic disease [median 0.247 L/day vs 0.326 L/day, respectively] [p <0.01]. There was no significant difference in ADA concentration between patients in endoscopic remission compared with those with recurrence [median 9.3 µg/mL vs 11.7 µg/mL, respectively]. Sustained CRP-based clinical remission and FC levels below 100 µg/g were generally associated with lower CL and higher ADA concentration. Repeated event analysis confirmed those findings with better performances of CL than concentration in associating with ER and other outcomes. Lower ADA clearance is associated with an improved clinical outcome for patients with Crohn's disease and may be a superior pharmacokinetic measure than concentration.

Abdominal pain is associated with an increased risk of future healthcare resource utilization in inflammatory bowel disease.

Numerous factors influence healthcare resource utilization (HRU) in inflammatory bowel disease (IBD). We previously demonstrated an association between the presence of certain IBD-related symptoms and HRU. We conducted a longitudinal study to identify the clinical variables and IBD-related symptoms predictive of HRU. This investigation utilized clinical encounters at an IBD center within a tertiary care referral center between 10/29/2015-12/31/2019. Participants were assessed over two time points (index and follow-up office visits) separated by a minimum of 6months. Demographics, endoscopic disease severity, totals and sub-scores of surveys assessing for IBD-related symptoms, HRU, and substance use, and IBD-related medications. HRU was defined as any IBD-related emergency room visit, hospitalization, or surgery during the 6months prior to follow-up appointment. We identified patients exhibiting HRU (at follow-up) and computed descriptive statistics and contingency table analyses of index appointment clinical data to identify predictors of HRU. Multivariable logistic regression models were fit incorporating significant demographic and clinical factors. 162 consecutively enrolled IBD patients (mean age 44.0years; 99f:63m; 115 Crohn's disease [CD], 45 ulcerative colitis [UC], 2 indeterminate colitis) were included. 121 patients (74.7%) exhibited HRU (mean age 43.6years; 73f:48m; 84 CD, 36 UC, 1 IC) preceding follow-up appointment. Abdominal pain (OR = 2.18, 95% CI 1.04-4.35, p = 0.04) at the index appointment was the only study variable significantly associated with HRU on bivariate analysis (Table 1). However, none of the clinical factors evaluated in this study were independently associated with HRU in our multivariable logistic regression model. In this longitudinal study, abdominal pain was the only clinical variable that demonstrated an association with future HRU (even when considering other symptoms and key variables such as disease activity, IBD-medications, and psychiatric comorbidities (i.e., anxious or depressed state). These findings reinforce the importance of regularly screening for and effectively treating abdominal pain in IBD.

Relationship of Sleep Health and Endoscopic Disease Activity in Inflammatory Bowel Disease: Endoscopic Disease Activity and Sleep.

Among adults with inflammatory bowel disease (IBD), self-reported sleep disturbances are associated with active symptoms, but the association between sleep measures and endoscopic disease activity is unknown. This study aimed to (1) compare sleep-wake behaviors among IBD patients based on endoscopic and clinical disease activity and (2) describe associations between actigraphy, self-reported sleep measures, and symptoms of fatigue, anxiety, and depression. Participants wore a wrist actigraph for 10 consecutive days and completed self-reported sleep questionnaires (Pittsburgh Sleep Quality Index [PSQI] and Patient-Reported Outcome Measures System [PROMIS] Sleep Disturbance and Sleep Interference questionnaires). Clinical and endoscopic disease activity were assessed. Based on actigraphic recordings ( n = 26), average total nighttime sleep was 437 minutes and sleep efficiency was 84%. Objective sleep measures did not differ based on endoscopic or clinical disease activity. Individuals with active clinical disease had higher PROMIS Sleep Disturbance (57.3 vs. 49.7, d = 1.28) and PROMIS Sleep-Related Impairment (58.1 vs. 52.8, d = 0.51) compared with those with inactive clinical disease. Self-reported sleep was significantly associated with anxiety, depression, and fatigue. Further research is needed to better characterize the relationship between sleep and endoscopic disease activity, and determine underlying mechanisms related to poor sleep in the IBD population.

Development of a scoring system for predicting the severity of ulcerative colitis

Background and study aimsMonitoring disease activity in ulcerative colitis (UC) is critical in preventing long-term complications. This study aims to develop a scoring system using non-invasive indicators to predict endoscopic activities for ulcerative colitis (UC) patients. Patients and methodsAll enrolled patients with UC admitted to Shanghai Xinhua Hospital between June 2017 and January 2021 were enrolled, and their clinical data were retrospectively collected and a number of serological biomarkers concentrations were analyzed. Patients were categorized into mild and moderate-to-severe disease groups. Univariate and multivariate logistic regression was used to predict moderate-to-severe endoscopic activities, which were then incorporated into a nomogram to establish a prediction scoring model. ResultOverall, 231 patients were divided into a mild group (n = 111, 48.0%) and a moderate-to-severe group (n = 120, 52.0%). The following variables were independently associated with the disease severity and were subsequently included into the prediction model: Proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA), C-reactive protein (CRP), hemoglobin(Hb), IL-10, stool frequency ≥ 5 times/day and hematochezia. Incorporating these 6 factors, the nomogram showed good discrimination with C-index of 0.819 and reliable calibration. A scoring model was established with the area under the curve 0.818. Moreover, PR3-ANCA and CRP correlated with the duration of hospital stay. ConclusionWe developed a predictive model for endoscopic disease activities by using noninvasive factors based on PR3-ANCA, CRP, Hb, IL-10, stool frequency and hematochezia. This prediction model might assist clinicians in managing patients with UC.

Multicenter prospective registration study of efficacy and safety of capsule endoscopy in Crohn’s disease in Japan (SPREAD-J study)

BackgroundEvidence of small-bowel capsule endoscopy (SBCE) for evaluating lesions in Crohn’s disease (CD) is lacking. We aimed to clarify the effectiveness and safety of SBCE in a large sample of patients with CD.MethodsThis multicenter prospective registration study recorded the clinical information and SBCE results of patients with definitive CD (d-CD) or suspected CD (s-CD). The primary outcomes were the rates of successful assessment of disease activity using SBCE, definitive diagnosis of CD, and adverse events. Secondary outcomes were the assessment of SBCE findings in patients with d-CD and s-CD and factors affecting SBCE incompletion and retention; and tertiary outcomes included the association between clinical disease activity or blood examination, endoscopic disease activity, ileal CD, and the questionnaire assessment of patient acceptance of SBCE.ResultsOf 544 patients analyzed, 541 underwent SBCE with 7 (1.3%) retention cases. Of 468 patients with d-CD, 97.6% could be evaluated for endoscopic activity. Of 76 patients with s-CD, 15.8% were diagnosed with ‘confirmed CD’. CD lesions were more frequently observed in the ileum and were only seen in the jejunum in 3.4% of the patients. Male sex and stenosis were risk factors for incomplete SBCE, and high C-reactive protein levels and stenosis were risk factors for capsule retention. In L1 (Montreal classification) patients, clinical remission was associated with endoscopic remission but showed low specificity and accuracy. The answers to the acceptability questionnaire showed the minimal invasiveness and tolerability of SBCE.ConclusionSBCE is practical and safe in patients with CD.

NAFLD Is Associated With Quiescent Rather Than Active Crohn's Disease.

Crohn's disease (CD) confers an increased risk of nonalcoholic fatty liver disease (NAFLD), but the pathogenesis remains poorly understood. We determined if active intestinal inflammation increases the risk of NAFLD in patients with CD. Two cohorts (2017/2018 and 2020) with CD and no known liver disease were enrolled consecutively during staging magnetic resonance enterography. We quantified proton density fat fraction, MaRIA (Magnetic Resonance Index of Activity), and visceral adipose tissue. NAFLD was diagnosed when proton density fat fraction ≥5.5%. Synchronous endoscopy was graded by the Simple Endoscopic Score for CD and Rutgeerts score, while clinical activity was graded by the Harvey-Bradshaw index. Cytokine profiling was performed for the 2020 cohort. Transient elastography and liver biopsy were requested by standard of care. NAFLD was diagnosed in 40% (n = 144 of 363), with higher prevalence during radiographically quiescent disease (odds ratio, 1.7; P = .01), independent of body mass index/visceral adipose tissue (adjusted odds ratio, 7.8; P = .03). These findings were corroborated by endoscopic disease activity, but not by aggregate clinical symptoms. Circulating interleukin-8 was independent of body mass index to predict NAFLD, but traditional proinflammatory cytokines were not. NAFLD subjects had similar liver stiffness estimates regardless of CD activity. Definitive or borderline steatohepatitis was present in most patients that underwent liver biopsy. Quiescent CD is associated with risk of NAFLD. These findings suggest potentially distinct pathogenic mechanisms of NAFLD in patients with CD compared with the prevailing leaky gut hypothesis proposed for individuals without inflammatory bowel disease. Future validation and mechanistic studies are needed to dissect these distinct disease modifying factors.

Mucosal α4β7+ Lymphocytes and MAdCAM+ Venules Predict Response to Vedolizumab in Ulcerative Colitis.

Therapeutic strategies for patients with ulcerative colitis (UC) are based on patient- and disease-related factors in combination with drug characteristics but fail to predict success in individual patients. A considerable proportion of UC patients do not respond to the biological vedolizumab. Therefore, pretreatment biomarkers for therapeutic efficacy are urgently needed. Mucosal markers related to the integrin-dependent T lymphocyte homing could be potent predictors. We prospectively included 21 biological- and steroid-naive UC patients with moderate-to-severe disease activity planned to escalate therapy to vedolizumab. At week 0, before initiating treatment, colonic biopsy specimens were obtained for immunophenotyping and immunohistochemistry. Clinical and endoscopic disease activity were determined at week 16 after 4 infusions of vedolizumab. In addition, we retrospectively included 5 UC patients who were first treated with anti-tumor necrosis factor α before receiving vedolizumab to compare with biological-naive patients. Abundance of α4β7 on more than 8% of all CD3+ T lymphocytes in colonic biopsies at baseline was predictive for responsiveness to vedolizumab (sensitivity 100%, specificity 100%). The threshold for the proportion of MAdCAM-1+ and PNAd+ of all venules in the biopsies predictive for responsiveness to vedolizumab was ≥2.59% (sensitivity 89%, specificity 100%) and ≥2.41% (sensitivity 61%, specificity 50%), respectively. At week 16, a significant decrease of α4β7+CD3+T lymphocytes was demonstrated in responders (18% [12%-24%] to 8% [3%-9%]; P = .002), while no difference was seen in nonresponders (4% [3%-6%] to 3%; P = .59). UC responders to vedolizumab have a higher percentage of α4β7+CD3+ T lymphocytes and a higher proportion of MAdCAM-1+ venules in colonic biopsies than nonresponders before initiating therapy. Both analyses could be promising predictive biomarkers for therapeutic response and may lead to more patient tailored treatment in the future.

Eosinophilic Esophagitis Histologic Scoring System: Correlation with Histologic, Endoscopic, and Symptomatic Disease and Clinical Use.

The eosinophilic esophagitis histologic scoring system (EoEHSS) was developed to enhance the diagnostic standard of peak eosinophil count (PEC) in evaluating disease activity in EoE. (1) Correlate the EoEHSS and PEC to measures of symptomatic and endoscopic disease activity, (2) Correlate EoEHSS grade and stage subcomponents to clinical, radiology, and endoscopic markers of fibrotic disease, (3) Evaluate EoEHSS remission in asymptomatic patients with PEC < 15 eosinophils per high powered field (eos/hpf). Secondary analysis of prospective cohort data of 22 patients with EoE that underwent dietary therapy and endoscopy at 3 time points. Active disease was defined by EoEHSS grade or stage > 0.125, symptomatic disease by EoE symptom activity index > 20, endoscopic disease by endoscopic reference score > 2, and histologic disease by PEC ≥ 15 eos/hpf. EoEHSS remission was defined by esophageal inflammation (EI) grade of 0-1, EI stage of 0, total grade ≤ 3, and total stage ≤ 3. EoEHSS grade and stage did not correlate with symptomatic disease but did with endoscopic and histologic disease. PEC showed similar correlation pattern. Abnormal grade and stage had strong sensitivity (87-100%) but poor specificity (11-36%) to detect symptomatic, endoscopic, and histologic disease activity. Lamina propria fibrosis was evaluated in 36% of biopsies and did not correlate with minimum esophageal diameter. Out of 14 patients who were in complete symptomatic, endoscopic, and histologic remission, 8 met criteria for EoEHSS remission. The positive and negative correlations of EoEHSS to specific measures of symptomatic, histologic, and endoscopic activity suggest that it provides complementary information in EoE.

Outcome of Biological Therapies and Small Molecules in Ulcerative Proctitis: A Belgian Multicenter Cohort Study

Several advanced therapies (biologic therapies and small molecules) have been approved for the treatment of moderate-to-severe ulcerative colitis. The registration trials for these agents typically excluded patients with isolated proctitis, leaving an evidence gap. We evaluated efficacy and safety of advanced therapies in patients with ulcerative proctitis (UP). This multicenter retrospective cohort study included consecutive patients with active UP (Mayo endoscopy subscore of ≥2, rectal inflammation up to 15 cm) initiating advanced therapy, after failing conventional therapy. The primary end point was short-term steroid-free clinical remission (total Mayo score ≤2 with no individual subscore >1). In addition, drug persistence and relapse-free and colectomy-free survival were assessed. Both binary logistic and Cox regression analyses were performed. In total, 167 consecutive patients (52.0% female; median age 41.0 years; 82.0% bionaive) underwent 223 courses of therapy for UP (38 adalimumab, 14 golimumab, 54 infliximab, 9 ustekinumab, 99 vedolizumab, 9 tofacitinib). The primary end point was achieved with 36.3% of the treatment courses, and based on multivariate analysis, more commonly attained in bionaive patients (P= .001), patients treated with vedolizumab (P= .001), patients with moderate endoscopic disease activity (P= .002), and a body mass index <25 kg/m2 (P= .018). Drug persistence was significantly higher in patients treated with vedolizumab (P < .001) and patients with a shorter disease duration (P= .006). No new safety signals were observed. Advanced therapies are also efficacious and safe in patients with ulcerative colitis limited to the rectum. Therefore, the inclusion of patients with UP in future randomized-controlled trials should be considered.

Semantic Segmentation of Gastric Polyps in Endoscopic Images Based on Convolutional Neural Networks and an Integrated Evaluation Approach.

Convolutional neural networks (CNNs) have received increased attention in endoscopic images due to their outstanding advantages. Clinically, some gastric polyps are related to gastric cancer, and accurate identification and timely removal are critical. CNN-based semantic segmentation can delineate each polyp region precisely, which is beneficial to endoscopists in the diagnosis and treatment of gastric polyps. At present, just a few studies have used CNN to automatically diagnose gastric polyps, and studies on their semantic segmentation are lacking. Therefore, we contribute pioneering research on gastric polyp segmentation in endoscopic images based on CNN. Seven classical semantic segmentation models, including U-Net, UNet++, DeepLabv3, DeepLabv3+, Pyramid Attention Network (PAN), LinkNet, and Muti-scale Attention Net (MA-Net), with the encoders of ResNet50, MobineNetV2, or EfficientNet-B1, are constructed and compared based on the collected dataset. The integrated evaluation approach to ascertaining the optimal CNN model combining both subjective considerations and objective information is proposed since the selection from several CNN models is difficult in a complex problem with conflicting multiple criteria. UNet++ with the MobineNet v2 encoder obtains the best scores in the proposed integrated evaluation method and is selected to build the automated polyp-segmentation system. This study discovered that the semantic segmentation model has a high clinical value in the diagnosis of gastric polyps, and the integrated evaluation approach can provide an impartial and objective tool for the selection of numerous models. Our study can further advance the development of endoscopic gastrointestinal disease identification techniques, and the proposed evaluation technique has implications for mathematical model-based selection methods for clinical technologies.

Delayed Ustekinumab Responders in Ulcerative Colitis Have Greater Inflammatory Burden but Similar Outcomes as Early Responders

Differences in 1-year outcomes among early compared with delayed responders to vedolizumab have been shown in ulcerative colitis. However, it is unclear whether similar differences exist with ustekinumab, and what factors differentiate delayed responders from nonresponders. This study was a post hoc analysis of patient-level data from the UNIFI clinical trial. Ustekinumab-treated patients with clinical response, defined as a reduction in total Mayo score of 30% or moreand 3 or more points from baseline with a reduction in their rectal bleeding subscore of 1 or more or a rectal bleeding subscore of 1 or less, at week 8 were deemed early responders andtheir outcomes were compared with delayed responders (week 8 nonresponders whosubsequently responded at week 16). The primary outcome assessed was 1-year clinical remission, defined as a total Mayo score of 2 or less and no subscore greater than1. We included 642 ustekinumab-treated patients, including 321 (50%) early responders, 115 (17.9%) delayed responders, and 205 (32.1%) nonresponders. No differences were observed for 1-year clinical remission among early vs delayed responders (132 of 321 [41.1%] vs 40 of 115 [34.8%]; P= .233), or for other outcomes assessed regardless of induction dose. Compared with early responders, delayed responders had more severe baseline Mayo endoscopic disease (88 of 115 [76.5%] vs 206 of 321 [64.2%]; P= .015) and abnormal baseline C-reactive protein level greater than 3 mg/L (83 of 115 [72.2%] vs 183 of 321 [57%]; P= .004). Compared with nonresponders, delayed responders had a significant decrease in C-reactive protein level (F-value [degrees of freedom, mean squares] [4, 844]; P < .0001) and fecal calprotectin level (F[4, 818]; P < .0001) through week16. Compared with early ustekinumab responders, delayed responders had a greater inflammatory burden at baseline. Early and delayed responders had similar 1-year outcomes. Biomarker decline observed in delayed responders can help differentiate them from nonresponders.

Correlations Between Gastrointestinal Symptoms and Endoscopic-Histologic Disease Activity in Adults with Ulcerative Colitis.

Discordance between gastrointestinal (GI) symptoms and endoscopic inflammation in patients with ulcerative colitis (UC) is known. However, the correlations between symptoms and endoscopic and histologic (endo-histologic) mucosal healing and remains unknown. We performed a secondary analysis of prospectively collected clinical, endoscopic, and histologic data on 254 colonoscopies from 179 unique adults at a tertiary referral center from 2014 to 2021. Spearman's rank was used to assess the correlation between patient reported outcomes and objective assessments of disease activity, as measured by validated instruments: Two-item patient-reported outcome measure (PRO-2) for stool frequency and rectal bleeding, the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) for endoscopic inflammation, and the Geboes score for histologic inflammation. The predictive value of objective assessments of inflammation and clinical symptoms was described using sensitivity, specificity, and positive/negative predictive value. One-quarter (28%, 72/254) of cases were in endo-histologic remission; of these, 25% (18/72) report GI symptoms (22% diarrhea; 6% rectal bleeding). Endo-histologically active disease had higher sensitivity (95% rectal bleeding; 87% diarrhea) and negative predictive value (94% rectal bleeding, 78% diarrhea) for clinically active disease compared to active disease on endoscopic (77%) or histologic assessment only (80%). The specificity of endo/histologic inflammation for GI symptoms was < 65%. PRO-2 was positively correlated with endoscopic disease activity (Spearman's rank 0.57, 95% CI 0.54-0.60, p < 0.0001) and histologic disease activity (Spearman's rank 0.49, 0.45-0.53, p < 0.0001). One-quarter of patients with ulcerative colitis in endo-histologic (deep) remission have gastrointestinal symptoms, more commonly with diarrhea than rectal bleeding. Endo-histologic inflammation has high sensitivity (≥ 87%) for diarrhea/rectal bleeding.

Clinical Utility of the Neutrophil-to-Bilirubin Ratio in the Detection of Disease Activity in Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic relapsing remitting form of inflammatory bowel disease (IBD). Current disease monitoring includes evaluation of symptoms, fecal calprotectin, and colonoscopy. Due to limited availability of the latter two modalities in China, we sought a readily available, inexpensive, disease monitoring laboratory assessment. We recently identified a novel serological index (the neutrophil-to-bilirubin ratio, NBR) for monitoring disease activity in Crohn's disease. However, the clinical significance has not been evaluated in UC. Here, we aimed to verify the hypothesis that NBR might be useful in monitoring clinical and endoscopic activity in patients with UC. To test our hypothesis, we conducted a single-center, retrospective study including a total of 188 patients with UC and 145 non-IBD controls. NBR was calculated to determine its practical value in monitoring disease activity (including clinical and endoscopic activity). Disease activity of UC was determined by the partial Mayo score and the Mayo endoscopic score (MES) system. NBR was significantly higher in patients with UC than that in controls (12.10, IQR: 9.85-16.69 versus 5.06, IQR: 3.94-6.55; p < 0.001) and showed positive correlations with clinical and endoscopic disease activity in UC. Additionally, NBR was significantly lower in patients with endoscopic mucosal healing (MH) than that in those without endoscopic MH (8.81, IQR: 6.67-11.67 versus 13.51, IQR: 11.04-18.71; p < 0.001). Serial evaluation of NBR in a subset of patients demonstrated that NBR was significantly decreased during the MH stage compared with that during the endoscopically active stage. Our study suggests that NBR may be a promising candidate for assessing disease activity in UC, with potential for widespread clinical use and significant clinical implications.

Bedside Intestinal Ultrasound Predicts Disease Severity and the Disease Distribution of Pediatric Patients With Inflammatory Bowel Disease: A Pilot Cross-sectional Study.

Intestinal ultrasound (IUS) is a noninvasive tool to assess bowel inflammation. There is a paucity of data on its accuracy in pediatric patients. The aim of this study is to evaluate the diagnostic performance of bowel wall thickness (BWT) measured using IUS compared with endoscopic disease activity in children suspected of having inflammatory bowel disease (IBD). We conducted a single-center cross-sectional pilot study of pediatric patients suspected to have previously undiagnosed IBD. Endoscopic inflammation was graded using segmental scores of the Simple Endoscopic Score for Crohn's Disease (SES-CD) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and classified as having healthy, mild, or moderate/severe disease activity. Association between BWT and endoscopic severity was assessed using the Kruskal-Wallis test. The diagnostic performance of BWT to detect active disease at endoscopy was evaluated using the area under the receiver operating characteristic curve; sensitivity and specificity were calculated. In all, 174 bowel segments in 33 children were assessed by IUS and ileocolonoscopy. An elevated median BWT was associated with increased bowel segment disease severity, classified by the SES-CD (P < .001) and the UCEIS (P < .01). Using a cutoff value of 1.9 mm, we found that the BWT had an area under the receiver operating characteristic curve of 0.743 (95% CI, 0.67-0.82), a sensitivity of 64% (95% CI, 53%-73%), and a specificity of 76% (95% CI, 65%-85%) to detect inflamed bowel. Increasing BWT is associated with increasing endoscopic activity in pediatric IBD. Our study suggests that the optimal BWT cutoff value for detecting active disease may be less than that seen in adults. Additional pediatric studies are needed.

Laboratory Data and IBDQ-Effective Predictors for the Non-Invasive Machine-Learning-Based Prediction of Endoscopic Activity in Ulcerative Colitis.

A suitable, non-invasive biomarker for assessing endoscopic disease activity (EDA) in ulcerative colitis (UC) has yet to be identified. Our study aimed to develop a cost-effective and non-invasive machine learning (ML) method that utilizes the cost-free Inflammatory Bowel Disease Questionnaire (IBDQ) score and low-cost biological predictors to estimate EDA. Four random forest (RF) and four multilayer perceptron (MLP) classifiers were proposed. The results show that the inclusion of IBDQ in the list of predictors that were fed to the models improved accuracy and the AUC for both the RF and the MLP algorithms. Moreover, the RF technique performed noticeably better than the MLP method on unseen data (the independent patient cohort). This is the first study to propose the use of IBDQ as a predictor in an ML model to estimate UC EDA. The deployment of this ML model can furnish doctors and patients with valuable insights into EDA, a highly beneficial resource for individuals with UC who need long-term treatment.

Usefulness of Serum Leucine-rich Alpha 2 Glycoprotein in Crohn's Disease: Is There Any Difference between Small Intestine and Colonic Lesions?

The usefulness of leucine-rich alpha 2 glycoprotein (LRG) to evaluate Crohn's disease (CD) activity differs among various intestinal lesions. We aimed to evaluate the association between endoscopic disease activity based on the Simple Endoscopic Score for Crohn's disease (SES-CD) and LRG level separately for small intestinal and colonic lesions. We examined the correlation between LRG level and SES-CD and performed receiver operating characteristic (ROC) analysis to determine the LRG cutoff value in 141 patients who underwent endoscopy (total 235 measurements). Furthermore, the LRG cutoff value was analyzed by comparing small intestinal and colonic lesions. LRG levels were significantly higher in patients without mucosal healing than in those with mucosal healing (15.9 μg/mL vs 10.5 μg/mL, P < .0001). The LRG cutoff value for mucosal healing was 14.3 μg/mL (area under the ROC curve [AUC]: 0.80; sensitivity: 0.89; specificity: 0.63). The LRG cutoff value for patients with type L1 was 14.3 μg/mL (sensitivity: 0.91; specificity: 0.53), and that for patients with type L2 was 14.0 μg/mL (sensitivity: 0.95; specificity: 0.73). The diagnostic performance (AUC) of LRG and C-reactive protein (CRP) for mucosal healing was, respectively, 0.75 and 0.60 (P = 0.01) in patients with type L1 and 0.80 and 0.85 (P = 0.90) in patients with type L2. The optimal LRG cutoff value for evaluating mucosal healing in CD is 14.3 μg/mL. LRG is more useful than CRP for predicting mucosal healing in patients with type L1. The superiority of LRG to CRP differs between small intestinal and colonic lesions.

Early fecal calprotectin levels at week 8 may guide therapeutic decisions on Ustekinumab therapy in patients with Crohn’s disease

Background Response evaluation after induction therapy with ustekinumab (UST) in Crohn’s disease (CD) is important for decisions on maintenance therapy. We aimed to assess the potential of fecal calprotectin (FC) levels to predict endoscopic response at week 16. Methods CD patients with FC >100 µg/g and endoscopic active disease (SES-CD> 2, Rutgeerts’ score ≥ i2) at initiation of UST therapy were enrolled. FC was determined at weeks 0, 2, 4, 8 and 16 and patients underwent a colonoscopy at week 16. The primary outcome was an endoscopic response at week 16 (SES-CD score ≥50% decrease or a decrease of ≥1 points in Rutgeerts’ score). The optimal cut-off levels of FC and change in FC to predict endoscopic response were determined using ROC statistics. Results 59 CD patients were included. Endoscopic response was observed in 21/59 (36%) patients. The diagnostic accuracy for FC levels at week 8 to predict endoscopic response at week 16 showed a predictive value of 0.71. A decrease in FC levels ≥500 µg/g between baseline at week 8 indicates endoscopic response (PPV = 89%), whereas absence of any decrease indicates endoscopic non-response after induction (NPV = 81%). Conclusions Continuation of UST therapy without endoscopic response evaluation may be considered in patients with a decrease in FC levels of ≥500 µg/g at week 8. The decision on continuation of UST therapy or therapy optimization needs reconsideration in patients without a decrease of FC level. In all other patients, endoscopic response evaluation of induction therapy remains essential for therapeutic decisions.